Haemophilia A is an inherited bleeding disorder caused by deficiency or dysfunction of coagulation factor VIII (FVIII) activity. The clinical manifestation is not on primary haemostasis—formation of the blood clot occurs normally—but the clot is unstable due to a lack of secondary thrombin formation. The disease is treated by intravenously injection of coagulation factor FVIII which is either isolated from blood or produced recombinantly.
Current treatment recommendations are moving from traditional on-demand treatment towards prophylaxis. The circulatory half life of endogenous FVIII bound to von Willebrandt Factor is 12-14 hours and prophylactic treatment is thus to be performed several times a week in order to obtain a virtually symptom-free life for the patients. IV administration is for many, especially children and young persons, associated with significant inconvenience and/or pain.
Various methods have been employed in the development of a Factor VIII variant with significantly prolonged circulatory half life. A number of these methods relate to conjugation of Factor VIII with hydrohphilic polymers such as e.g. PEG (poly ethylene glycol).
There is thus a need in the art for novel Factor VIII products with factor VIII activity that comprise one or more of the following features: preferably homogenous in structure, preferably safe, preferably biologically degradable, and preferably have a significantly prolonged circulatory half life in order to reduce the number of factor VIII administration per week. There is likewise a need in the art for relatively simple methods for providing such molecules.